2026/03/01 by Radoslava Sivkova, Monika Matiyani, Gabriela S. García-Briones +7 · 1 voice
Biochemistry, Genetics and Molecular Biology · Chemistry · #Advanced Polymer Synthesis and Characterization #Hydrogels: synthesis, properties, applications #RNA Interference and Gene Delivery
paper · pdf · doi:10.1021/acsapm.5c04108
openalex publication_date 2026/03/01 · openalex created_date 2026/03/02 · openalex updated_date 2026/06/15
High Resolution Image Download MS PowerPoint Slide Synthetic polycations are key components for engineering polyelectrolyte complexes with wide-ranging biomedical potential. However, the high cytotoxicity of fully charged polycations remains a major limitation for clinical applications. To address this challenge, we report on polycations derived from the cationic monomer 2-( N,N -dimethylaminoethyl) acrylate (DMAEA), which gradually loses charge through hydrolysis, thereby reducing their charge density over time. The overall charge fraction (from 100% to 20%) was further controlled through copolymerization with the neutral comonomer 2-hydroxyethyl acrylate (HEA). The selected conditions of reversible addition–fragmentation chain transfer (RAFT) copolymerization, specifically protonation of DMAEA with trifluoroacetic acid to mask its tertiary amino groups, enabled a precise control over the characteristics of the copolymers (termed D/H) up to 75% conversions, with close agreement between theoretical and experimental molecular weights up to 100 000 g/mol, consistently low dispersities (<1.2), and an excellent match between the theoretical and actual copolymer compositions. Hydrolysis studies at pH 7.4 showed that increasing the HEA content in D/H copolymers from 20 to 50 mol % led to only a 10% increase in the hydrolysis over 3 weeks. Isothermal titration calorimetry analysis demonstrated that all copolymers retained their ability to complex with heparin, with binding strength comparable to that of commonly used polycations. Importantly, the cytotoxicity of D/H copolymers toward human umbilical vein endothelial cells (HUVECs) decreased with increasing HEA content, reaching more than 80% cell viability at a relatively high concentration of 30 μg/mL. These findings demonstrate that D/H copolymers combine precise structural control with reduced cytotoxicity, making them promising candidates for biomedical polyelectrolyte platforms.